title: Antimicrobial activity and SAR study of new gemini imidazolium-based chlorides.
abstract: A series of 70 new 3,3'(α,ω-dioxaalkyl)bis(1-alkylimidazolium) chlorides were synthesized. They were characterized with respect to surface active properties and antimicrobial activity against the following pathogens: Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Candida krusei, and Candida albicans. In this article, besides description of the synthesis, we characterize a set of features of these compounds, concerning their structure (described by the length of the dioxaalkan spacer and the length of the alkyl substituent in the aromatic ring) and surface active properties (critical micelle concentration, value of surface tension at critical micelle concentration, value of surface excess, molecular area of a single particle, and free energy of adsorption of molecule). Then, we present a SAR study for Staphylococcus aureus, as one of the most widespread pathogenic strains, conducted with the help of the Dominance-based Rough Set Approach (DRSA), that involves identification of relevant features and relevant combinations of features being in strong relationship with a high antimicrobial activity of the compounds. The SAR study shows, moreover, that the antimicrobial activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds.
authors.affiliation: Department of Pharmaceutical Technology, Nicolaus Copernicus University, Jurasza 2, 85-094, Bydgoszcz, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Pałkowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Błaszczyński
authors.forename: Andrzej
authors.initials: A
authors.lastname: Skrzypczak
authors.forename: Jan
authors.initials: J
authors.lastname: Błaszczak
authors.forename: Karolina
authors.initials: K
authors.lastname: Kozakowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Wróblewska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kożuszko
authors.forename: Eugenia
authors.initials: E
authors.lastname: Gospodarek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Krysiński
authors.forename: Roman
authors.initials: R
authors.lastname: Słowiński
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D002712:Chlorides; D007093:Imidazoles; C029899:imidazole
keywords: cheminformatics; drug design; structure-based drug design